Abstract
Multicentric carpo-tarsal osteolysis syndrome (MCTO) is a rare skeletal disorder commonly caused by MAF bZIP transcription factor B (MAFB) mutation. Clinically, it is characterized by aggressive osteolysis, which mainly affects the carpal tarsal bones, and is frequently associated with progressive nephropathy. Since the painful swelling and motion limitation on the wrists and/or ankles of MCTO mimics those of juvenile idiopathic arthritis (JIA), very often, MCTO is misdiagnosed as JIA. Here, we report two MCTO patients initially diagnosed with JIA but showed no response to treatment: P1, with a medical history of more than 10 years, was presented with a typical triad of arthritis-osteolysis-nephropathy; while P2 showed oligoarthritis. Gene tests were then taken and revealed a novel mutation, p.P63Q, and a previously reported conversion, p.S54L, in the MAFB gene. We also summarized the clinical and genetic features of a cohort containing 49 genetically confirmed MCTO patients. All 51 gene-confirmed MCTO cases (49 identified from the literature plus two patients identified herein) developed the disease during childhood. The median delay in diagnosis was 3.83 years (0–35 years). All cases presented bony lesions, and two-thirds had secondary renal lesions (32/48; three unknown), half of which (16/32) progressed into renal failure. Almost two-thirds (34/51), 75% (38/51), and 71% (36/51) of patients had no record of eye problems, facial abnormalities, and other manifestations. Most were misdiagnosed as JIA but didn't respond to treatment. Based on our experience, we suggest that clinicians should comprehensively evaluate the involvement of multiple systems in JIA patients, especially the kidney and eyes. And for JIA patients who underwent more than 3-month treatment with Bio-DMARD, genetic tests are recommended when they show little/no clinical and imaging changes, their high disease activity remains, and their disease activity remission is <50%, especially when combined with a triad of arthritis-osteolysis-nephropathy.
Highlights
Multicentric carpo-tarsal osteolysis syndrome (MCTO, OMIM#166300) is a rare skeletal disorder characterized by early childhood onset of aggressive osteolysis, which significantly affects the carpal and tarsal bones, as well as other large joints such as the elbow and knee joints [1]
MCTO is often misdiagnosed as juvenile idiopathic arthritis (JIA), especially as oligoarthritis because the painful swelling and motion limitation on the wrists and/or ankles of MCTO mimics those of JIA
Apart from the triad of arthritis-osteolysis-nephropathy, joint involvement in MCTO patients usually begins from the wrist or ankle, which is rarely seen in oligoarticular JIA
Summary
Multicentric carpo-tarsal osteolysis syndrome (MCTO, OMIM#166300) is a rare skeletal disorder characterized by early childhood onset of aggressive osteolysis, which significantly affects the carpal and tarsal bones, as well as other large joints such as the elbow and knee joints [1]. The gene test results coupled with the typical clinical manifestations led to a diagnosis of MCTO He was treated with Denosumab (a single dose of 60 mg) at 13 years and 3 months old; 1 month later, his joint pain almost disappeared. He received two doses of the TNFα receptor inhibitor (infliximab), whereupon the pain, and swelling in the wrists were relieved, but the range of motion (active and passive) in the wrist joints worsened. Gender Age at onset of bone lesions Age at MCTO diagnosis Diagnostic delay Age at onset of renal lesions Age at onset of renal failure Family history Bone lesions Joints (except wrists and ankles) affected Renal lesions Renal failure Eye problems Facial abnormality Other manifestations Treatment NSAIDs DMARDs TNFα inhibitors Denosumab ACEI Calcium supplements MAFB variants Inherited derivation. MCTO, Multicentric carpo-tarsal osteolysis syndrome; NSAIDs, Non-steroidal antiinflammatory drugs; DMARDs, Disease-modifying antirheumatic drugs; MAFB, MAF bZIP transcription factor B; MTX, Methotrexate; LEF, Leflunomide; SSZ, Sulfasalazine; TNF α, Tumor necrosis factor-α; ACEI, Angiotensin-Converting Enzyme Inhibitors
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
